Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal Women: Women's Health Initiative Memory Study | Dementia and Cognitive Impairment | JAMA | JAMA Network
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1.
Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer disease in the US population: prevalence estimates using the 2000 census.  Arch Neurol.2003;60:1119-1122.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12925369&dopt=AbstractGoogle Scholar
2.
Lopez OL, Jagust WJ, DeKosky ST.  et al.  Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1.  Arch Neurol.2003;60:1385-1389.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14568808&dopt=AbstractGoogle Scholar
3.
Fisk JD, Merry HR, Rockwood K. Variations in case definition affect prevalence but not outcomes of mild cognitive impairment.  Neurology.2003;61:1179-1184.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14610117&dopt=AbstractGoogle Scholar
4.
Henderson VW, Paganini-Hill A, Emanuel CK.  et al.  Estrogen replacement therapy in older women: comparison between Alzheimer disease cases and nondemented control groups.  Arch Neurol.1994;51:896-900.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8080389&dopt=AbstractGoogle Scholar
5.
Waring SC, Rocca WA, Petersen RC, O'Brien PC, Tangalos EG, Kokmen E. Postmenopausal estrogen replacement therapy and risk of AD: a population-based study.  Neurology.1999;52:965-970.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10102413&dopt=AbstractGoogle Scholar
6.
Steffens DC, Norton MC, Plassman BL.  et al.  Enhanced cognitive performance with estrogen use in nondemented community-dwelling older women.  J Am Geriatr Soc.1999;47:1171-1175.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10522948&dopt=AbstractGoogle Scholar
7.
Kawas C, Resnick SM, Morrison A.  et al.  A prospective study of estrogen replacement therapy and the risk of developing Alzheimer disease: the Baltimore Longitudinal Study on Aging.  Neurology.1997;48:1517-1521.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9191758&dopt=AbstractGoogle Scholar
8.
Tang MX, Jacobs D, Stern Y.  et al.  Effect of estrogen during menopause on risk and age at onset of Alzheimer disease.  Lancet.1996;348:429-432.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8709781&dopt=AbstractGoogle Scholar
9.
Jacobs DM, Tang MX, Stern Y.  et al.  Cognitive function in nondemented older women who took estrogen after menopause.  Neurology.1998;50:368-373.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9484355&dopt=AbstractGoogle Scholar
10.
Yaffe K, Sawaya G, Lieberburg I, Grady D. Estrogen therapy in postmenopausal women: effects on cognitive function and dementia.  JAMA.1998;279:688-695.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9496988&dopt=AbstractGoogle Scholar
11.
Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD. Postmenopausal hormone replacement: scientific review.  JAMA.2002;288:872-881.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12186605&dopt=AbstractGoogle Scholar
12.
Matthews K, Cauley J, Yaffe K, Zmuda JM. Estrogen replacement therapy and cognitive decline in older community women.  J Am Geriatr Soc.1999;47:518-523.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10323642&dopt=AbstractGoogle Scholar
13.
Barrett-Connor E, Kritz-Silverstein D. Estrogen replacement therapy and cognitive function in older women.  JAMA.1993;269:2637-2641.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8487446&dopt=AbstractGoogle Scholar
14.
Henderson VW, Paganini-Hill A, Miller BL.  et al.  Estrogen for Alzheimer disease in women: randomized, double-blind, placebo-controlled trial.  Neurology.2000;54:295-301.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10668686&dopt=AbstractGoogle Scholar
15.
Mulnard RA, Cotman CW, Kawas C.  et al.  Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease.  JAMA.2000;283:1007-1015.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10697060&dopt=AbstractGoogle Scholar
16.
Wang PN, Liao SQ, Liu RS.  et al.  Effects of estrogen on cognition, mood, and cerebral blood flow in AD: a controlled study.  Neurology.2000;54:2061-2066.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10851363&dopt=AbstractGoogle Scholar
17.
Hogervorst E, Williams J, Budge M, Riedel W, Jolles J. The nature of the effect of female gonadal hormone replacement therapy on cognitive function in post-menopausal women: a meta-analysis.  Neuroscience.2000;101:485-512.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11113299&dopt=AbstractGoogle Scholar
18.
LeBlanc ES, Janowsky J, Chan BK, Nelson HD. Hormone replacement therapy and cognition: systematic review and meta-analysis.  JAMA.2001;285:1489-1499.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11255426&dopt=AbstractGoogle Scholar
19.
Shumaker SA, Reboussin BA, Espeland MA.  et al.  The Women's Health Initiative Memory Study (WHIMS): a trial of the effect of estrogen therapy in preventing and slowing the progression of dementia.  Control Clin Trials.1998;19:604-621.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9875839&dopt=AbstractGoogle Scholar
20.
Writing Group for the Women's Health Initiative Investigators.  Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial.  JAMA.2002;288:321-333.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12117397&dopt=AbstractGoogle Scholar
21.
Women's Health Initiative Steering Committee.  Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial.  JAMA.2004;291:1701-1712.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15082697&dopt=AbstractGoogle Scholar
22.
The Women's Health Initiative Study Group.  Design of the Women's Health Initiative clinical trial and observational study.  Control Clin Trials.1998;19:61-109.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9492970&dopt=AbstractGoogle Scholar
23.
Teng EL, Chui H. The Modified Mini-Mental State (3MS) examination.  J Clin Psychiatry.1987;48:314-318.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3611032&dopt=AbstractGoogle Scholar
24.
Shumaker SA, Legault C, Rapp SR.  et al.  Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.  JAMA.2003;289:2651-2662.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12771112&dopt=AbstractGoogle Scholar
25.
Morris JC, Heyman A, Mohs RC.  et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD), part I: clinical and neuropsychological assessment of Alzheimer disease.  Neurology.1989;39:1159-1165.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2771064&dopt=AbstractGoogle Scholar
26.
Spitzer RL, Williams JB, Kroenke K.  et al.  Utility of a new procedure for diagnosing mental disorders in primary care: the PRIME-MD 1000 study.  JAMA.1994;272:1749-1756.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7966923&dopt=AbstractGoogle Scholar
27.
Burke WJ, Roccaforte WH, Wengel SP. The short form of the Geriatric Depression Scale: a comparison with the 30-item form.  J Geriatr Psychiatry Neurol.1991;4:173-178.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1953971&dopt=AbstractGoogle Scholar
28.
American Psychiatric Association.  Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, DC: American Psychiatric Association; 1994.
29.
Petersen RC, Doody R, Kurz A.  et al.  Current concepts in mild cognitive impairment.  Arch Neurol.2001;58:1985-1992.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11735772&dopt=AbstractGoogle Scholar
30.
Ganguli M, Belle S, Ratclliff G.  et al.  Sensitivity and specificity for dementia of population-based criteria for cognitive impairment: the MoVIES project.  J Gerontol.1993;48:M152-M161.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8315228&dopt=AbstractGoogle Scholar
31.
Cox DR. Regression models and life tables.  J R Stat Soc B.1972;34:187-220.Google Scholar
32.
Sherwin BB. Estrogen and cognitive functioning in women.  Endocr Rev.2003;24:133-151.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12700177&dopt=AbstractGoogle Scholar
33.
Bethea CL, Lu NZ, Gundlah C, Streicher JM. Diverse actions of ovarian steroids in the serotonin neural system.  Front Neuroendocrinol.2002;23:41-100.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11906203&dopt=AbstractGoogle Scholar
34.
Linzmayer L, Semlitsch HV, Saletu B.  et al.  Double-blind, placebo-controlled psychometric studies on the effects of a combined estrogen-progestin regimen versus estrogen alone on performance, mood and personality of menopausal syndrome patients.  Arzneimittelforschung.2001;51:238-245.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11304940&dopt=AbstractGoogle Scholar
35.
US Food and Drug Administration.  FDA Updates Hormone Therapy Information for Post Menopausal Women. Available at: http://www.fda.gov/bbs/topics/NEWS/2004/NEW01022.html.
36.
Zandi PP, Carlson MC, Plassman BL.  et al.  Hormone replacement therapy and the incidence of Alzheimer disease in older women: the Cache County Study.  JAMA.2002;288:2123-2129.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12413371&dopt=AbstractGoogle Scholar
37.
Beck TJ, Stone KL, Oreskovic TL.  et al.  Effects of current and discontinued estrogen replacement therapy on hip structural geometry: the Study of Osteoporotic Fractures.  J Bone Miner Res.2001;16:2103-2110.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11697807&dopt=AbstractGoogle Scholar
38.
Gibbs RB. Estrogen replacement enhances acquisition of a spatial memory task and reduces deficits associated with hippocampal muscarinic receptor inhibition.  Horm Behav.1999;36:222-233.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10603286&dopt=AbstractGoogle Scholar
39.
Rapp PR, Morrison JH, Roberts JA. Cyclic estrogen replacement improves cognitive function in aged ovariectomized rhesus monkeys.  J Neurosci.2003;23:5708-5714.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12843274&dopt=AbstractGoogle Scholar
40.
Petersen RC, Jack Jr CR, Xu YC.  et al.  Memory and MRI-based hippocampal volumes in aging and AD.  Neurology.2000;54:581-587.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10680786&dopt=AbstractGoogle Scholar
41.
Vermeer SE, Koudstaal PJ, Oudkerk M, Hofman A, Breteler MMB. Prevalence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study.  Stroke.2002;33:21-25.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11779883&dopt=AbstractGoogle Scholar
42.
Bryan RN, Wells SW, Miller TJ.  et al.  Infarctlike lesions in the brain: prevalence and anatomic characteristics at MR imaging of the elderly—data from the Cardiovascular Health Study.  Radiology.1997;202:47-54.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8988191&dopt=AbstractGoogle Scholar
43.
Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal PJ, Breteler MMB. Silent brain infarcts and the risk of dementia and cognitive decline.  N Engl J Med.2003;348:1215-1222.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12660385&dopt=AbstractGoogle Scholar
44.
Kuller LH, Lopez OL, Newman A.  et al.  Risk factors for dementia in the Cardiovascular Health Cognition Study.  Neuroepidemiology.2003;22:13-22.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12566949&dopt=AbstractGoogle Scholar
45.
Swan GE, DeCarli C, Miller BL.  et al.  Association of midlife blood pressure to late-life cognitive decline and brain morphology.  Neurology.1998;51:986-993.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9781518&dopt=AbstractGoogle Scholar
46.
Launer LJ, Masaki K, Petrovitch H, Foley D, Havlik RJ. The association between midlife blood pressure levels and late-life cognitive function: the Honolulu-Asia Aging Study.  JAMA.1995;274:1846-1851.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7500533&dopt=AbstractGoogle Scholar
47.
Longstreth Jr WT, Dulberg C, Manolio TA.  et al.  Incidence, manifestations, and predictors of brain infarcts defined by serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study.  Stroke.2002;33:2376-2382.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12364724&dopt=AbstractGoogle Scholar
48.
Neuropathology Group of the Medical Research Council Cognitive Function and Aging Study (MRC CFAS).  Pathological correlates of late-onset dementia in a multicentre community-based population in England and Wales.  Lancet.2001;357:169-175.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11213093&dopt=AbstractGoogle Scholar
49.
Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer disease: the Nun Study.  JAMA.1997;277:813-817.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9052711&dopt=AbstractGoogle Scholar
50.
Iadecola C, Gorelick PB. Converging pathogenic mechanisms in vascular and neurodegenerative dementia.  Stroke.2003;34:335-337.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12574528&dopt=AbstractGoogle Scholar
Original Contribution
June 23/30, 2004

Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal Women: Women's Health Initiative Memory Study

Author Affiliations

Author Affiliations: Departments of Public Health Sciences (Drs Shumaker, Legault, and Coker) and Psychiatry and Behavioral Medicine (Dr Rapp), Wake Forest University School of Medicine, Winston-Salem, NC; Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pa (Dr Kuller); Department of Neurosciences, University of California at San Diego (Dr Thal); Department of Preventive Medicine, State University of New York at Stony Brook (Dr Lane); Institute for the Study of Aging, New York, NY (Dr Fillit); Stanford Prevention Research Center, Stanford University, Stanford, Calif (Dr Stefanick); Department of Obstetrics and Gynecology, Wayne State University School of Medicine/Hutzel Hospital, Detroit, Mich (Dr Hendrix); Department of Medicine, University of Alabama at Birmingham (Dr Lewis); Department of Geriatric Medicine, University of Hawaii, Honolulu (Dr Masaki).

JAMA. 2004;291(24):2947-2958. doi:10.1001/jama.291.24.2947
Abstract

Context The Women's Health Initiative Memory Study (WHIMS) previously found increased risk for dementia and no effect on mild cognitive impairment (MCI) in women treated with conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA).

Objective To determine the effects of CEE alone and CEE plus MPA on incidence of probable dementia and MCI in older women.

Design, Setting, and Participants Randomized, double-blind, placebo-controlled clinical trials of CEE (estrogen-alone trial) or CEE plus MPA (estrogen plus progestin trial) in community-dwelling women aged 65 to 79 years, conducted from June 1995 to July 8, 2002 (estrogen plus progestin; n = 4532), or to February 29, 2004 (estrogen-alone; n = 2947), in 39 of the 40 WHI clinical centers.

Interventions In the estrogen-alone trial, 1 daily tablet containing either 0.625 mg/d of CEE vs matching placebo; in the estrogen plus progestin trial, 1 daily tablet containing CEE (0.625 mg/d) plus MPA (2.5 mg/d) vs matching placebos.

Main Outcome Measures Probable dementia and MCI.

Results In the estrogen-alone trial, 47 participants were diagnosed with probable dementia, of whom 28 were assigned to CEE and 19 to placebo (hazard ratio [HR], 1.49; 95% confidence interval [CI], 0.83-2.66). Incidence rates for probable dementia in the estrogen-alone trial were statistically similar to those in the estrogen plus progestin trial (45 vs 22 per 10 000 person-years for CEE plus MPA vs placebo, respectively; P = .11). When data were pooled per the original WHIMS protocol, the overall HR for probable dementia was 1.76 (95% CI, 1.19-2.60; P = .005). After excluding participants with baseline Modified Mini-Mental State Examination scores at or below the screening cut point, the HR was 1.77 (95% CI, 0.74-4.23; P = .20) in the estrogen-alone trial and 2.19 (95% CI, 1.25-3.84; P = .006) in the pooled trials. In the estrogen-alone trial, 76 participants were diagnosed with MCI in the CEE group vs 58 in the placebo group (HR, 1.34; 95% CI, 0.95-1.89). In the combined trial data, the HR was similar (1.25; 95% CI, 0.97-1.60). In the estrogen-alone trial, 93 participants receiving CEE were diagnosed with either probable dementia or MCI vs 69 receiving placebo (HR, 1.38; 95% CI, 1.01-1.89; P = .04).

Conclusions Estrogen therapy alone did not reduce dementia or MCI incidence and increased the risk for both end points combined. Pooling data for estrogen alone and estrogen plus progestin resulted in increased risks for both end points. Use of hormone therapy to prevent dementia or cognitive decline in women 65 years of age or older is not recommended.

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